Asymptomatic carriers of hepatitis B virus (HBV) have a very high risk of developing primary hepatocellular carcinoma (PHC). The risk ratio for carriers is greater than 200 and the lifetime probability for developing-PHC is 40% (in Taiwan and probably elsewhere). A large body of data supports the hypothesis that altering the carrier state can considerably decrease the risk of liver cancer. Therefore, the carrier state for HBV, which can be readily measured by a simple serological test, can be regarded both as a "treatable" risk factor and an "intermediate endpoint" for the development of PHC. In previous studies we and others have shown that extracts of plants of the genus Phyllanthus inhibit the DNA polymerase of HBV and related viruses. Fractions containing this active principle have been identified and a tentative chemical structure has been proposed. Purified active principle is not currently available for clinical trials and probably will not be for several years. Extracts of the whole plant eliminate or decrease the amounts of woodchuck hepatitis virus (WHV) in woodchuck carriers. In a preliminary retrospective analysis, this treatment appears to decrease the frequency of cancer in the treated animals. In a preliminary human clinical trial, 60% of treated human carriers lost HBV, which did not return, while only 4% of the controls did so. We propose a clinical trial in human HBV carriers. Animal toxicity studies will first be done and then a phase I trial in humans. This will be followed by an efficacy trial on 10 carriers and a controlled trial involving 90 carriers. Based on the preliminary human trials, this should give sufficient power to detect a significant difference between treated and controls. We also propose a trial of the medication in woodchuck carriers to determine if treatment not only removes the risk factor but also if this change in the "intermediate endpoint" will decrease the risk of cancer.